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<article xmlns:xlink="http://www.w3.org/1999/xlink">
  <front>
    <journal-meta>
      <journal-title-group>
        <journal-title>Birmingham, UK
∗ Corresponding author.
† These authors contributed equally.
oliyura@gmail.com (Y. Oliinyk); marichka.v.richtsi@gmail.com (M. Kapshuk) ; leonid.oliinyk@gmail.com (L. Oliinyk)</journal-title>
      </journal-title-group>
    </journal-meta>
    <article-meta>
      <title-group>
        <article-title>Software for anomaly detection in MRI images⋆</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Yurii Oliinyk</string-name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Mariia K</string-name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>pshuk</string-name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Leonid Oliinyk</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>Kaunas University of Technology</institution>
          ,
          <addr-line>K. Donelaičio St. 73, Kaunas, 44249</addr-line>
          ,
          <country country="LT">Lithuania</country>
        </aff>
        <aff id="aff1">
          <label>1</label>
          <institution>National Technical University of Ukraine “Igor Sikorsky Kyiv Polytechnic Institute”</institution>
          ,
          <addr-line>Beresteiskyi Ave. 37, Kyiv, 03056</addr-line>
          ,
          <country country="UA">Ukraine</country>
        </aff>
      </contrib-group>
      <pub-date>
        <year>2023</year>
      </pub-date>
      <volume>000</volume>
      <fpage>0</fpage>
      <lpage>0002</lpage>
      <abstract>
        <p>This article discusses the development of the algorithm and software for detecting the anomalies in MRI images. The main goal of the research is to increase the efficiency and the rate of disease diagnosis by creating a user-friendly and functional application for automatic anomaly detection. Anomaly detection algorithms were researched and software efficiency was tested. .NET platform, HD-BET tool, and ResNet model were chosen for the software development.</p>
      </abstract>
      <kwd-group>
        <kwd>eol&gt;Anomaly detection</kwd>
        <kwd>neural networks</kwd>
        <kwd>machine learning</kwd>
        <kwd>software</kwd>
        <kwd>MRI</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>1. Introduction</title>
      <p>
        Magnetic resonance imaging (MRI) is a modern examination method that uses magnetic fields and
radio waves to create detailed images of internal organs and tissues. The strong magnetic field
created by an MRI scanner causes the atoms in the body to align in one direction. Radio waves are
then sent from the MRI machine and move these atoms from their original position. When the radio
waves are turned off, the atoms return to their original position and send radio signals. These
signals are received by the computer and converted into an image of the examined body part, and
the image appears on the monitor [
        <xref ref-type="bibr" rid="ref1">1</xref>
        ].
      </p>
      <p>
        The main advantage of MRI compared to other methods, such as computed tomography or X-ray
examination, is that it does not require the use of ionizing radiation, which makes it safe for
patients. Also, MRI better defines the difference between types of soft tissues, and between normal
and abnormal soft tissues [
        <xref ref-type="bibr" rid="ref1">1</xref>
        ].
      </p>
      <p>
        Today, the development of IT technologies allows the use of artificial intelligence and machine
learning to automate the analysis of medical images, including MRI images. In general, there are
three main areas for the use of artificial intelligence in radiology: image reconstruction and
enhancement, image classification and segmentation, and diagnostic support. The first direction is
the most developed, while the other two are less studied, as they have more requirements for the
accuracy of the results [
        <xref ref-type="bibr" rid="ref2">2</xref>
        ].
      </p>
      <p>In terms of the classification of MRI images, with the help of machine learning, most studies
focus on the detection of specific diseases or certain pathologies. For example, the detection of brain
tumors. Such studies are more narrowly focused and more precise, but they require a large set of
specific training data. Typically, these data studies use supervised learning, which requires labels on
the data. Another direction is the detection of pathologies in general, comparing an unhealthy case
with the norm. Such studies have a wider application, since they do not focus on specific cases, and
can use different approaches.</p>
      <p>However, there are some drawbacks to the current state of things. First of all, there is a small
number of studies and their limited use. It is also important to take into account such disadvantages
as the limited accuracy of some algorithms, the instability of the software and the high cost of some
solutions. To improve the situation, it is worth introducing a light and open solution that would
ensure reliability and have a low cost of implementation and maintenance.</p>
      <p>That is why this study is dedicated to the development of software for detecting pathologies on
MRI images with a convenient user interface and the use of unsupervised machine learning
methods for anomaly detection. The development of the software aligns with the United Nations'
Sustainable Development Goals, particularly the third goal: Good Health and Well-being. By
enhancing early diagnosis and improving healthcare efficiency, this technology leads to better
health outcomes, reducing mortality rates and enabling more equitable access to quality healthcare.</p>
    </sec>
    <sec id="sec-2">
      <title>1.1. Related Work</title>
      <p>
        While supervised DL learns to explicitly distinguish between what is normal and what is abnormal,
unsupervised anomaly detection makes no assumptions about the concept of anomalies.
Unsupervised methods either make no assumptions about the data at all and determine the
probability of samples containing abnormal specimens, or have no knowledge of what exactly
represents the abnormality, but clearly can determine the normal distribution of healthy anatomy
[
        <xref ref-type="bibr" rid="ref3">3</xref>
        ].
      </p>
      <p>
        The detection of anomalies can be attributed to the problem of clustering. One of the most used
algorithms is K-Means clustering. This is a very simple algorithm that groups data into clusters
based on similar features. It is also worth noting that K-Means is an algorithm that is based on
distance and requires careful selection of parameters, in particular, the selection of features that
should be taken into account when grouping. Although the K-Means algorithm is widely used for
data clustering, it also has its drawbacks, especially when applied to the problem of anomaly
detection. Primarily, K-Means assumes that all points in the data set belong to some cluster, making
it unable to effectively recognize anomalous clusters that may be separated or misrepresented. Also,
the algorithm is very sensitive to the presence of outliers in the input data. Large outliers can affect
the location of the centroids and lead to incorrect clustering [
        <xref ref-type="bibr" rid="ref4">4</xref>
        ].
      </p>
      <p>
        Another approach is to use an autoencoder (AE), another type of unsupervised learning. They
consist of a so-called encoder, which maps a high-dimensional input signal to a low-dimensional
hidden (latent) space, and a decoder, which has the task of restoring or reconstructing the input [
        <xref ref-type="bibr" rid="ref3">3</xref>
        ].
AEs can be different, but convolutional ones are the most common.
      </p>
      <p>
        Variational autoencoders (VAE) are one of the variations of AE, which includes Bayesian
variational methods in the usual architecture. The main difference is how they model the
distribution of the input data in the latent space. The main disadvantage of AE is that the latent
space can be extremely irregular. VAEs solve this problem because instead of a single point in the
latent space, they return a distribution [
        <xref ref-type="bibr" rid="ref3 ref5">3, 5</xref>
        ].
      </p>
      <p>
        Another important part of autoencoder modeling is the choice of the encoder and decoder
architecture. Some of the most common models for feature extraction are the Convolutional Neural
Network (CNN), Residual Neural Network (ResNet), and Recurrent Neural Network (RNN). The
architecture of a regular CNN consists of an input layer that is subsequently convoluted using a
combination of convolutional filters followed by an output layer. It is very efficient and widespread,
but as the network depth increases and a certain threshold is reached, the error rate starts to
increase because of the gradient vanishing and degradation. Another type is RNNs, which are
designed to interpret temporal or sequential information. The main difference is that they reuse the
activations of previous or subsequent nodes in the sequence. However, the problem of gradient
vanishing remains in this type of networks. ResNet is a modification of CNN that introduces a
residual learning function into the architecture. Therefore, unlike CNN, ResNet is able to solve the
problem of accuracy loss, because this model additionally uses skip connection, i.e. direct
connection, between layers. This allows it to take activation from one level and transfer it to
another level, thus preserving parameters at deeper layers [
        <xref ref-type="bibr" rid="ref6 ref7">6, 7</xref>
        ].
      </p>
    </sec>
    <sec id="sec-3">
      <title>1.2. Research Tasks</title>
      <p>Main goals: improving the efficiency and speed of diagnosing diseases by creating a convenient and
functional application for the automatic recognition of anomalies. The following tasks should be
solved within this research:
 development of software for anomaly detection in MRI images
 development of the anomaly detection algorithm
 researching anomalies algorithm and software efficiency</p>
    </sec>
    <sec id="sec-4">
      <title>2. The Software Development</title>
      <p>The following describes the steps for the development of software for anomaly detection in MRI
images.</p>
    </sec>
    <sec id="sec-5">
      <title>2.1. Software Architecture</title>
      <p>The software uses a layered architecture and consists of three projects (packages):
MRIVision.Python, MRI-Vision.Domain and MRI-Vision.UI. The package diagram is shown in Figure 1.</p>
      <p>The MRI-Vision.Python project is small and handles the model, images, and image analysis. It
primarily includes classes for designing, creating, and using an autoencoder model as well as its
training, which includes working with images – reading, preprocessing, and analysis.</p>
      <p>The MRI-Vision.Domain project provides the functionality to process the results obtained from
MRI-Vision.Python. It uses the third-party Python.NET project in order to integrate Python code
into .NET. Additionally, since all methods calling Python code are called asynchronously and due to
the GIL (Global Interpreter Lock) in Python, there is a separate module that performs all Python
tasks in one thread.</p>
      <p>The MRI-Vision.UI package contains only pages and additional GUI functionality for presenting
the processed results obtained from MRI-Vision.Domain.</p>
    </sec>
    <sec id="sec-6">
      <title>2.2. IDE and Additional Software Libraries</title>
      <p>The most important part of creating a neural network is selecting the language and framework to
be used in the development. Python is the most widely used programming language in the industry
with a large selection of frameworks and libraries. The choice of a framework which will be used to
train the neural network is another part. The most common in the field are Keras, PyTorch, and
TensorFlow. Keras is a high-level interface that makes it easy to quickly build and train the models.
TensorFlow offers more flexibility and control, making it popular among experienced researchers.
PyTorch combines the simplicity of Keras with the flexibility of TensorFlow, offering dynamic
graph definition and GPU computing acceleration. Moreover, PyTorch provides a user-friendly
interface for working with dynamic graphs, simplifying the process of changing the model
architecture during experiments. Due to the mentioned facts, PyTorch was chosen for the
development.</p>
      <p>
        Yet another crucial part of neural network training is data preprocessing. MRI data are usually
represented as 3D models converted into slices. Many auxiliary libraries are widely used in DL and
the medical field. One such library is the open-source MONAI platform, which offers a selection of
optimised implementations of various DL algorithms and utilities specifically designed for medical
visualisation tasks. It provides tools for flexible preprocessing of multidimensional medical image
data [
        <xref ref-type="bibr" rid="ref8">8</xref>
        ]. Compared to NiBabel, which simply offers read-and-write access to common medical
image formats like NIfTI and DICOM, MONAI is more feature-rich [
        <xref ref-type="bibr" rid="ref9">9</xref>
        ].
      </p>
      <p>
        When working with MRI brain images, another useful tool for preprocessing is technologies that
offer functionality for automated brain extraction of consecutive MRI images. Several alternatives
perform this task using artificial neural networks [
        <xref ref-type="bibr" rid="ref10">10</xref>
        ]. A full comparison of known alternatives is
presented in Table 1.
      </p>
      <p>
        For this work, HD-BET was chosen since it is more accurate and faster than other alternatives
such as MONSTR, 3DSkullStrip, BEaST, etc [
        <xref ref-type="bibr" rid="ref10">10</xref>
        ].
      </p>
      <p>
        Given that the software is aimed at easy use by healthcare professionals, it is essential to develop
a user-friendly and straightforward graphical interface. Although Python provides a wide range of
libraries for GUI development, the C# programming language was selected due to its better
performance, especially for applications that require fast real-time response. For this work, the
Windows Presentation Foundation (WPF) framework was chosen since it uses a more modern
XAML-based layout approach compared to its WinForms counterpart. There are two versions of
WPF – on the .NET platform and on the .NET Framework platform. The .NET platform is used in
this paper considering it has superior performance, availability, reliability, and tools [
        <xref ref-type="bibr" rid="ref11">11</xref>
        ].
      </p>
      <p>Furthermore, Visual Studio Code for Python development was selected as an IDE since it is
lightweight and has a large selection of additional extensions for viewing images, opening
TensorBoard in order to view training statistics, etc. For C# development, Visual Studio was chosen,
which has a user-friendly interface for developing WPF applications. Examples of the user interface
are shown in Figure 2 and Figure 3.</p>
    </sec>
    <sec id="sec-7">
      <title>2.3. Choosing and Training of the Neural Network</title>
      <p>Comparing the algorithmic solutions presented in the Related Work section in this paper the
decision to design an autoencoder was made considering it has higher accuracy compared to
KMeans. Additionally, since the model only needs to recognise anomalies without generating new
ones, an autoencoder is a better choice than a variational autoencoder, given it is easier to learn and
use. ResNet was chosen as the architecture of the autoencoder because of its advantage over
conventional CNNs and RNNs in training deep neural networks for image feature recognition and
extraction.</p>
      <p>The neural network consists of an encoder, a decoder and a latent space between them. The
encoder is composed of a convolutional input layer and five ResNet units for downsampling, each
with three convolutional groups: two consecutive convolutional layers and a feedforward
connection. Three consecutive steps make up each convolutional group – Conv3d convolution,
ReLU activation, and BatchNorm3d normalisation. To stabilise the gradient and prevent the
exploding gradient problem, normalisation is utilised. The number of channels in each block is 32,
64, 128, 256, and 512. Thus, the latent space is 1024. The architecture of the decoder is inversely
symmetric, with upsampling layers used in place of downsampling ones.</p>
      <p>The anomaly detection autoencoder is based on the fact that if the AC is trained only on healthy
samples, the model will be able to reconstruct only them. Therefore, when an anomalous instance is
received as input, the reconstruction error will be much higher in the anomalous areas, since the
anomaly will not be reconstructed.</p>
      <p>
        The model should be trained on healthy MRI brain images. Healthy samples were taken from
the IXI dataset which contains almost 600 MRI brain images of normal, healthy subjects [
        <xref ref-type="bibr" rid="ref12">12</xref>
        ].
Twothirds of the data are used for training, and the remaining data are used to evaluate the model after
each epoch. The Adam optimiser with PyTorch was used for optimisation with a learning rate of
103. MSELoss, which measures the mean square error between the input and reconstructed data, was
used to compute the loss. The training was performed on GPU and CPU by parallelising the data
using PyTorch's nn.DataParallel class, which significantly reduced the training time.
      </p>
      <p>During training, 400 epochs were performed, since after 350 epochs the loss almost did not
decrease. Figure 4 shows a plot of the change in the value of the loss function after each epoch.</p>
      <p>Thus, by the end of training, the loss function value was 0.0003. Moreover, after each epoch, if
the model was determined to be the best of all the previous ones, it is saved to the file. Thus, the last
best model was the model from the 388th epoch (Figure 4). It is this model that is used in the
software.</p>
    </sec>
    <sec id="sec-8">
      <title>2.4. Data Structure Description</title>
      <p>
        The program accepts an MRI image as an input – a compressed file with the NIfTI (Neuroimaging
Informatics Technology Initiative) extension. Therefore, the final extension looks like .nii.gz. This
extension is widely used for storing MRI brain images. Its particular advantage for this application
is that, unlike DICOM files, the NIfTI format stores much less metadata that is not needed for model
training. This makes NIfTI files lighter in size and faster to read [
        <xref ref-type="bibr" rid="ref13">13</xref>
        ]. Also, this type of input data is
set due to the use of HD-BET which only accepts this extension type as input. NIfTI images are
registered in a local coordinate system, and each file contains metadata and 3D pixels in seven
dimensions. Typically, NIfTI files have the extension .nii or .nii.gz and can be split into a binary
header (.hdr) and image data (.img or .img.gz) [
        <xref ref-type="bibr" rid="ref14">14</xref>
        ]. Figure 5 shows a diagram of the general
structure of an NIfTI file.
      </p>
      <p>In addition, there are numerous different types of MRI images. By default, each examination
includes T1-weighted and T2-weighted images, and other types such as FLAIR (FLuid Attenuation
Inversion Recovery), DWI (Diffusion-Weighted Imaging), etc. may be included as well. Liquids
appear dark in T1-weighted images, while grey matter appears darker than white matter. In
contrast, fluids appear light in T2-weighted images, and grey matter appears lighter than white
matter. Various pathologies, such as inflammation, necrosis, tumours, etc., cause high fluid content
in these areas, making them prominent on T2-weighted images.</p>
      <p>In this work, T2-weighted images were chosen since they are included in the standard set of
images created during examinations and since various pathologies are clearly visible on them,
unlike T1-weighted images.</p>
      <p>As an output, the user receives analysis results which can be downloaded as PNG images.</p>
    </sec>
    <sec id="sec-9">
      <title>2.5. Anomaly Detection Algorithm</title>
      <p>The general steps of the algorithm used to detect anomalies on the selected file are as follows:
1. Upload a file
2. Change the image orientation (if necessary)
3. Resize the image (if necessary)
4. Collapse image data into latent space
5. Reconstruct an image from the latent space
6. Calculate the reconstruction error value as the absolute difference between the input and
reconstructed images
7. Calculate the anomaly value of each image slice
8. Create images with anomalous areas for each image slice
9. Display the analysis results
Figure 6 shows the anomaly detection algorithm in a diagram form.</p>
      <p>In the 6th step, the reconstruction error for each pixel is calculated using the following formula:</p>
      <p>A ' ijk =|I ijk − R ijk |, (1)
whereI ijk is the pixel value of the input image,R ijk is the pixel value of the reconstructed image.</p>
      <p>In the 7th step, the total anomaly value for each slice is calculated using the following formula:
A i =
∑ A ijk</p>
      <p>,</p>
      <p>N − n (A ijk )
where A i is the slice anomaly value, A ijk is the pixel anomaly, n (A ijk ) is the number of
anomalous pixels,N is the number of pixels in the slice. Thus, slices with a larger anomaly area will
have a higher anomaly value. The pixel anomaly value is obtained from the reconstruction error
using the following formula:</p>
      <p>A ijk ={A 0'i,jkif, Aif A'ijk' i&lt;jk t&gt;t , (3)
where t is the maximum reconstruction error value that is allowed and is not considered an
anomaly.</p>
      <p>The algorithm produces a list of anomaly values for each slice, which is presented in the form of
a line chart and an image of the slices with the anomalous areas highlighted.
(2)</p>
    </sec>
    <sec id="sec-10">
      <title>3. The Software and Algorithm Efficiency</title>
    </sec>
    <sec id="sec-11">
      <title>3.1. Researching the Accuracy of Anomaly Detection</title>
      <p>
        The BraTS2020 dataset, which consists of a large number of clinically validated glioblastoma and
glioma brain MRI images, was used to determine this metric. The dataset contains NIfTI files
(.nii.gz) of type T1, T1Gd, T2, FLAIR and a file with segmented pathology, which were selected
manually by specialists [
        <xref ref-type="bibr" rid="ref15 ref16 ref17">15, 16, 17</xref>
        ].
      </p>
      <p>
        To determine the accuracy of the model, 369 files from the dataset were analyzed and the value
of the reconstruction error was obtained for each of them. The average reconstruction error,
obtained when using the model on fully healthy specimens, was then subtracted from each
reconstruction error to obtain an image of the anomaly. Healthy specimens, on which the model
was also trained, were taken from the IXI dataset [
        <xref ref-type="bibr" rid="ref12">12</xref>
        ]. The obtained results were then compared
with the segmented image for the same image. The use of only IXI and BraTS2020 datasets in the
study may limit the findings’ general applicability. To improve the results’ generalizability, future
research should include more datasets that represent a broader range of MRI imaging and clinical
situations.
      </p>
      <p>The results were recorded as:
 correctly detected abnormal areas (true positive value)
 incorrectly detected abnormal areas (false positive value)
 correctly detected healthy areas (true negative value)
 incorrectly detected healthy areas (false negative value)</p>
      <p>Precision shows the number of correctly selected abnormal areas to all selected abnormal areas,
so it indicates how many of the abnormal areas it classified correctly. Recall indicates the number of
correctly selected anomalous areas to all areas that should be selected as anomalous, that is, how
many anomalous areas were selected and not missed. The F1 score is a harmonic mean between
precision and recall, and shows how accurate and reliable the result is. Accuracy shows the extent
to which the abnormality map of the MRI image in general corresponds to the truth. All metrics
take values between 0 and 1, with higher values implying better results.</p>
      <p>Table 2 shows the values of the metrics in percentages.</p>
      <p>Thus, the software identifies 82% of anomalies, and the overall accuracy of detecting anomalies
in images is 89%.</p>
    </sec>
    <sec id="sec-12">
      <title>3.2. Evaluating Software Efficiency</title>
      <p>To research software efficiency , two test runs were performed: model training of 5 epochs and
processing of 200 MRI images. Additionally, using GPU increases model training speed by more
than 15 times, but at the same time increases image processing speed only by 22%.</p>
    </sec>
    <sec id="sec-13">
      <title>4. Discussion and Conclusion</title>
      <sec id="sec-13-1">
        <title>Model training, s (5 epochs)</title>
        <p>The result of this research was the development of the algorithm and the convenient and functional
application for the automatic detection of anomalies on MRI images. The software’s overall
accuracy in detecting anomalies in images is 89%, with 82% of anomalies detected. The total time of
analysis takes less than 7 seconds, proving the software’s efficiency and speed. The software also
has a user-friendly and intuitive user interface that makes it easy to view MRI images and analysis
results.</p>
        <p>The anomaly detection algorithm is based on the fact that if AE is trained only on healthy
samples, then the model will be able to reconstruct only them. Therefore, when an instance with an
anomaly is received at the input, the reconstruction error will be much higher in the anomalous
areas, since the anomaly will not be reconstructed correctly. Thus, having the reconstruction error
for each pixel, it is possible to determine how large its abnormality value is for each slice, which is
then can be presented in the form of a line chart and an image of the slices with the anomalous
areas highlighted.</p>
        <p>The software uses a multi-layered architecture and consists of three projects (packages):
MRIVision.Python, MRI-Vision.Domain, and MRI-Vision.UI.</p>
        <p>The model was trained on healthy MRI brain images. Healthy samples were taken from the IXI
dataset which includes almost 600 MRI brain images of normal, healthy subjects. Two-thirds of the
data are used for training, and the remaining data are used to evaluate the model’s performance
after each epoch. The training was performed on GPU and CPU by parallelising the data using
PyTorch’s nn.DataParallel class, which significantly reduced the training time. The 388th epoch
model was the last best model. The anomaly detection algorithm consists of nine steps and produces
a list of anomaly values for each slice, which is presented in the form of a line chart and an image of
the slices with the anomalous areas highlighted. Using GPU increases model training speed more
than 15 times, but at the same time, it increases image processing speed by only 22%.</p>
        <p>The software’s further development includes support for more MRI image file formats, for
example, the support for DICOM files. Extending the neural network library to analyse MRI images
of other parts, such as images of the spinal cord, various joints, chest, etc., is another promising
improvement. Support for simultaneously analysing numerous files would be a further addition. A
useful improvement to enhance the graphical user interface would be the ability to generate a
3Dprojection and view the image in different angles in several windows. It is worth considering the
possibility of multifactorial analysis using different types of images (T1, T2, FLAIR, etc.) in order to
increase the software’s accuracy.</p>
        <p>To guarantee that the proposed software is practical and clinically relevant, extensive user
testing and validation must be considered. in authentic clinical contexts. To enhance the evidence
supporting the model’s robustness, it is critical to evaluate its performance across a broader and
more diverse dataset.</p>
      </sec>
    </sec>
    <sec id="sec-14">
      <title>Declaration on Generative AI</title>
      <sec id="sec-14-1">
        <title>The authors have not employed any Generative AI tools.</title>
      </sec>
    </sec>
  </body>
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